AIM: To investigate the effects of astragalus injection combined with puerarin injection on endo-plasmic reticulum stress through PERK pathway in diabetic nephropathy mice .METHODS: Male KKAy mice were ran-domly divided into model group ( injected with normal saline ) and treatment group ( injected with astragalus and puerarin ) . The male C57BL/6J mice served as normal group .The mice were sacrificed 4 weeks after treatments for observing morpho-logical changes under electron microscope .The renal tissues were collected to determine the expression of protein kinase R-like endoplasmic reticulum kinase ( PERK ) , eukaryotic initiation factor 2α( eIF2α) and glucose-regulated protein 78 (GRP78) at mRNA and protein levels by real-time PCR and Western blot.RESULTS: Under electron microscope, the renal tubular epithelial cells in model group and treatment group showed the swelling of the nucleus , endoplasmic reticulum and mitochondria .The results of real-time PCR and Western blot showed that the expression of PERK , eIF2αand GRP78 at mRNA and protein levels in model group was higher than that in normal group (P<0.05), while that in treatment group was lower than that in model group .CONCLUSION: Astragalus injection combined with puerarin injection reduces the mRNA and protein expression of PERK , eIF2αand GRP78, thus inhibiting the endoplasmic reticulum stress in type 2 dia-betic mice to protect the kidney function .