〔Abstract〕 Objective To study the effects and mechanisms of paeoniflorin-6′-O-benzenesulfonate(CP-25) on the proliferation of mesangial cells(MCs) induced by angiotensin(Ang) Ⅱ. Methods The mesangial cell line SV40 MES 13 was cultured in vitro and stimulated with Ang Ⅱ(50 nmol/L) for 2 days. CP-25(10, 100, 1 000 nmol/L) was added at same time. After co-cultured 48 h, the proliferation of MCs was measured by high-content imaging microscope. The protein expression levels of GRK2 and phosphorylated p38(p-p38) in MCs were detected by Western blot. The fluorescence signaling of GRK2 and p-p38 protein was measured with laser confocal microscope and its colocalization rates were analyzed. The proportion of GRK2 into the cytoplasm was detected with cytometer imaging flow. Results Compared to the control group, the results showed that Ang Ⅱ could significantly promote the MCs proliferation,increase the protein expression levels of GRK2 and p-p38,up-regulate the colocalization rates of GRK2 and p-p38,and increase the proportion of GRK2 into the cytoplasm. CP-25( 10,100,1 000 nmol/L) could inhibit the proliferation induced by Ang Ⅱ to varying degrees,reduce the protein expression levels of GRK2,p-p38 and the co-localization rates of GRK2 and p-p38,and down-regulate the ratios of GRK2 into cytoplasm. Conclusion CP-25 can inhibit MCs' proliferation stimulated with Ang Ⅱ,and its mechanism may be related to GRK2/p38 MAPK signaling pathway.