OBJECTIVE: To investigate the combinatorial effects of Naomai Yihao (NMYH) Capsules and vascular endothelial growth factor (VEGF) gene-transfected bone marrow mesenchymal stem cells (BMSCs) on angiogenesis in cerebral ischemic tissues in rats and the mechanism. METHOD: BMSCs were isolated and cultured from bone marrow by an adherence method. Then, BMSCs were transfected with the eukaryotic expression plasmid pEGFP-VEGF165 by positive ionic liposome transfection. A rat model of middle cerebral artery occlusion (MCAO) was established. Rats were allocated to six groups: model, BMSC, VEGF gene-transfected BMSC transplantation (BMSC/ VEGF), NMYH, combined NMYH and BMSC/VEGF (combined treatment group) and sham operation groups. The behavioral rating score (BRS) of rats and the expression of CD34 and VEGF in brain tissue were measured by immunohistochemistry on days 7, 14 and 21 after reperfusion. Angiogenesis was observed and evaluated with laser scanning confocal microscopy. RESULTS: The BRS of rats in NMYH, BMSC transplantation and combined treatment groups was significantly lower than that of the model group (P< 0.001), with no significant difference between NMYH and transplantation groups (P=0.619). The expression of CD34 and VEGF in NMYH, transplantation and combined treatment groups increased (P< 0.001), with a significant difference between NMYH and transplantation groups (P<0.001). The blood vessel area in NMYH, transplantation and combined treatment groups was significantly increased (P<0.05), without a significant difference between NMYH and transplantation groups (P=0.873). CONCLUSIONS: VEGF gene-transfected BMSCs improve angiogenesis in the cerebral ischemic area. NMYH Capsules promote angiogenesis in MCAO rats treated with BMSC transplantation, which show an improved BRS. The mechanism of angiogenesis may be related to up-regulation of VEGF expression. © 2012 JTCM. All rights reserved.