AIM: To study the relationship between interleu-kin-1beta (IL-1β) up-regulating tissue inhibitor of matrix metalloproteinase-1 (TIMMP-1) mRNA expression and phosphorylation of both c-jun N-terminal kinase (JNK) and p38 in rat hepatic stellate cells (HSC). METHODS: RT-PCR was performed to measure the expression of TIMMP-1 mRNA in rat HSC. Western blot was performed to measure IL-1β-induced JNK and p38 activities in rat HSC. RESULTS: TIMMP-1 mRNA expression (1.191±0.079) was much higher after treatment with IL-1β(10 ng/mL) for 24 h than in control group (0.545±0.091) (P<0.01). IL-1βactivated JNK and p38 in a time-dependent manner. After stimulation with IL-1βfor 0, 5, 15, 30, 60 and 120 min, the JNK activity was 0.982±0.299, 1.501±0.720, 2.133±0.882, 3.360±0.452, 2.181±0.789, and 1.385±0.368, respectively. There was a significant difference in JNK activity at 15 min (P<0.01), 30 min (P<0.01) and 60 min (P<0.01) in comparison to that at 0 min. The p38 activity was 1.061±0.310, 2.050±0.863, 2.380±0.573, 2.973±0.953, 2.421±0.793, and 1.755±0.433 at the 6 time points (0, 5, 15, 30, 60 and 120 min) respectively. There was a significant difference in p38 activity at 5 min (P<0.05), 15 min (P<0.01), 30 min (P<0.01) and 60 min (P<0.01) compared to that at 0 min. TIMMP-1 mRNA expression trended to decrease in 3 groups pretreated with different concentrations of SP600125 (10μmol/L, 1.022±0.113; 20μmol/L, 0.869±0.070; 40μmol/L, 0.666±0.123). Their decreases were all significant (P<0.05, P<0.01,P<0.01) in comparison to control group (without SP600125 treatment, 1.163±0.107). In the other 3 groups pretreated with different concentrations of SB203580 (10μmol/L, 1.507±0.099; 20μmol/L, 1.698±0.107; 40μmol/L, 1.857±0.054), the expression of TIMMP-1 mRNA increased. Their levels were higher than those in the control group (without SB203580 treatment, 1.027±0.061) with a significant statistical significance CONCLUSION: IL-1βhas a direct action on hepatic fi-brosis by up-regulating TIMMP-1 mRNA expression in rat HSC. JNK and p38 mitogen-activated protein kinases (MAPKs) are involved in IL-1β-induced TIMMP-1 gene expression, and play a distinct role in this process, indicating that p38 and JNK pathways cooperatively mediate TIMP-1 mRNA expression in rat HSC. AIM: To study the relationship between interleu-kin-1beta (IL-1β) up-regulating tissue inhibitor of matrix metalloproteinase-1 (TIMMP-1) mRNA expression and phosphorylation of both c-jun N-terminal kinase (JNK) in rat hepatic stellate cells (HSC). METHODS: RT-PCR was performed to measure the expression of TIMMP-1 mRNA in rat HSC. Western blot was performed to measure IL-1β-induced JNK and p38 activities in rat HSC. TIMP-1 mRNA expression (1.191 ± 0.079) was much higher after treatment with IL-1β (10 ng / mL) for 24 h than in control group (0.545 ± 0.091) (P <0.01) a time-dependent manner. After stimulation with IL-1βfor 0, 5, 15, 30, 60 and 120 min, the JNK activity was 0.982 ± 0.299, 1.501 ± 0.720, 2.133 ± 0.882, 3.360 ± 0.452, 2.181 ± 0.789, and 1.385 ± 0.368, respectively. There was a significant difference in JNK activity at 15 min (P <0.01), 30 min (P <0.01) and 60 min 1.061 ± 0.31 0, 2.050 ± 0.863, 2.380 ± 0.573, 2.973 ± 0.953, 2.421 ± 0.793, and 1.755 ± 0.433 at the 6 time points (0, 5, 15, 30, 60 and 120 min) respectively. There was a significant difference in p38 Activity at 5 min (P <0.05), 15 min (P <0.01), 30 min (P <0.01) and 60 min (P <0.01) compared to that at 0 min. TIMMP-1 mRNA expression trended to decrease in 3 groups were pretreated with different concentrations of SP600125 (10 μmol / L, 1.022 ± 0.113; 20 μmol / L, 0.869 ± 0.070; 40 μmol / L, 0.666 ± 0.123) ) in comparison with control group (without SP600125 treatment, 1.163 ± 0.107). In the other 3 groups pretreated with different concentrations of SB203580 (10 μmol / L, 1.507 ± 0.099; 20 μmol / L, 1.698 ± 0.107; 40 μmol / L, 1.857 ± 0.05), the expression of TIMMP-1 mRNA increased. Their levels were higher than those in the control group (without SB203580 treatment, 1.027 ± 0.061) with a significant statistical significance CONCLUSION: IL-1βhas a direct action on hepatic fi-brosis by up-regulating TIMMP-1 mRNA expression in rat HSC. JNK and p38 mitogen-activated protein kinases (MAPKs) are involved in IL-1β-induced TIMMP-1 gene expression, and play a distinct role in this process, indicating that p38 and JNK pathways cooperatively mediate TIMP -1 mRNA expression in rat HSC.