Aim To investigate the effects of rosiglitazone on the proliferation of vascular smooth muscle cells induced by angiotensinⅡ(AngⅡ) and possible mechanism. Methods Vascular smooth muscle cells(VSMC) were isolated from aortic media of four-week-old male Sprague-Dawley rats by enzymatic digestion and cultured in monolayer.VSMC in passage 4～8 in log phase were used in following experiments.VSMC were treated by 1 μmol/L AngⅡ for 6 h and randomly divided into the groups as follows: control group(10% FBS in DMEM),Ang Ⅱ group(1 μmol/L AngⅡ),groups respectively treated with different concentration of rosiglitazone(20,30,40 and 50 μmol/L) for 12 h and groups respectively treated with 30 μmol/L rosiglitazone for 6,12,18 and 24 h.The VSMC growth,change of proliferation cycle and mRNA and protein expression of AngⅡ type 2 receptor(AT2R) in all groups were detected by using MTT colorimetric assay,FCM,RT-PCR and Western blotting. Results The mean absorbance(A value) in the VSMC treated by AngⅡ was significantly higher as compared with that of the control group(P><0.01).The A values were markedly reduced in the VSMC treated by different concentration of rosiglitazone for 12 h or 30 μmol/L rosiglitazone for 6,12,18 and 24 h(P><0.05 or P><0.01).The proliferation index(PI) and S-phase fraction(SPF) in the AngⅡ group were significantly higher than those of the control group(P><0.01).With the increase in rosiglitazone concentration and prolongation of treatment time,PI and SPF were greatly reduced(P><0.05 or P><0.01).Compared with the AngⅡ group,expression of AT2R mRNA and protein in the VSMC with the treatment of 20,30 and 50 μmol/L rosiglitazone for 12 h or of 30 μmol/L rosiglitazone for 6,12 and 24 h were both markedly increased(P><0.05 or P><0.01),reaching a maximum in 50 μmol/L rosiglitazone for 12 h or 30 μmol/L rosiglitazone for 24 h. Conclusions Rosiglitazone inhibited VSMC proliferation induced by AngⅡ at least partially through up-regulating expression of AT2R both at mRNA and protein levels in a concentration-dependent and time-dependent manner,in order to play vasculoprotective role.