Background and Objective: Hepatic stellate cells ( HSC ) are a non-parenchymal cells of liver, located in Disse gap, around the Liver sinusoid. Activation and proliferation of Hepatic stellate cells leads to hepatic fibrosis,p38MAPK signaling pathway has a role in regulating cell proliferation, at present there are few studies with the relationship between p38MAPK pathway and the proliferation of hepatic stellate cells. To explore the p38MAPK activity and cell proliferation of acetaldehyde- induced rat’s hepatic stellate cell (HSC) dealt with SB203580.Methods: Cultivate rats’HSC strains in vitro,Setting blank group, acetaldehyde control group and SB203580 group.l0% calf serum DMEM medium is added to the blank group,200μmol/L acetaldehyde is added to l0% calf serum DMEM medium in the acetaldehyde control group, on the basis of aldehyde group,different concentrations SB203580 is added to SB203580 group. Morphological changes of HSC were observed under microscope .The proliferation of HSC was evaluated by MTT colorimetric assay and the variability of p-p38 was examined by Westem-blot, SABC measured rate of c-myc protein positive.Result: P38 activity increases in acetaldehyde-induced HSC, and cell proliferated significantly; SB203580(5,10,20μmol/L) can block the activity of p38 in the cells, and inhibit acetaldehyde-induced HSC proliferation(p<0.05),when increased the concentration to 30μmol/L,its inhibitive effect on HSC proliferation was more significant(p<0.01),and the expression of p-p38 decreased relatively(p<0.05), While c-myc protein expression rate is gradually reduced.Conclusion: Inhibition of p38MAPK activity can affect HSCs’proliferation, p38 signaling pathway may play an important role in the regulation of HSC proliferation,and it’s mechanism have a relationship with the affection of the expression of c-myc gene.