Objective    To explore the effects and mechanism of Butaprost (PGE2 receptor 2 agonist) on proliferation and secretion of extracellular matrix (ECM) accumulation induced by TGF-β1 in mouse mesangial cell.    Methods    Mouse golmerular mesangial cell (GMC) were divided into 5 groups: control group; TGF-β1 group; TGF-β1 plus Butaprost group (10, 1, 0.1 μmol/L). The proliferation of GMCs was measured by CCK-8, the proportion of G2＋S phase in the cell cycle was measured by flow cytometry and cAMP, PGE2 secreted into media by ELISA assay. The expression of LN, FN, CTGF, COX1, COX2, p27 protein and mRNA was measured by Western blot and real time quantitative reverse PCR, phosphorylation of p38 MAPK was measured by Western blot as well.    Results   TGF β1 induced the proliferation of GMCs and increased the secretion of cAMP and PGE2 as well as the proportion of G2＋S phase. Besides, TGF β1 significantly upregulated the expression of FN, LN, CTGF, COX2 and phosphorylated p38 MAPK mRNA and protein while the expression of p27Kip1 mRNA and protein was reduced (all P＜0.05). Butaprost effectively reversed above changes and their activities (all P＜0.05). All the effects of Butaprost were dose-dependent.    Conclusions    Butaprost may inhibit TGF-β1-induced cell proliferation and ECM accumulation by upregulate the expression of cAMP and repress the activity of p38 MAP kinase thus decreased the expression of COX2, PGE2, FN, LN and CTGF.