Objective To investigate the influence of somatostatin (SS) and protein tyrosine enzyme 1 B (PTP1B) on the proliferation and the matrix protein secretion and phosphorylation of JAK2/STAT3 of hepatic stellate cells (HSC) induced by leptin. Methods The effect of different concentrations of SS on the proliferation of activatied HSCs induced by leptin was detected with MTT assay. HSCs were divided into control group, leptin group, leptin+10-7 mol/LSS group, leptin+10-6 mol/LSS group, TIMP-1, type I collagen and PTP1B protein and mRNA. Phosphorylation of JAK2/STAT3 were detected by RT-PCR, Western bolt and ELISA assay. Results SS could promote leptin-induced proliferation of HSCs in a dose-adependent manner. SS can improve PTP1B protein and mRNA, and higher does of SS could render more increase compared with the lower does. SS could reduce TIMP-1 mRNA, type I collagen mRNA and protein expression, and make the JAK2/STAT3 dephosphorylated, and the higher SS group reduce these factors more obviously than the lower group. Conclusion SS up-regulates PTP1B expression, inhibits JAK2/STAT3 signal transduction, proliferation, and reduces TIMP-1, I collagen expression in actived HSCs induced by leptin.