Objective To investigate the effect of ShenQiWan on diabetic renal injury and evaluate whether the mechanism of ShenQiWan is to reduce endoplasmic reticulum stress via the protein kinase R-like endoplasmic reticulum kinase (PERK) pathway. Methods Twenty 12-week-old male ZDF ( fa / fa) rats were randomly divided into the model group (n= 10) and SQW group (n= 10). Seven male ZDF (fa / +) rats of the same age were used as the control group. The SQW group was given ShenQiWan decoction ( 8. 12 g / kg), whereas the control and model groups were given an equivalent volume of normal saline. During the intervention period, the general state of the rats was recorded, the fasting blood glucose concentration was measured regularly and the 24 h urinary microalbumin concentration was tested. To observe the pathological changes, paraffin sections of renal tissue were stained with periodic acid Schiff, Masson blue, and periodic acid methenamine silver-hematoxylin and eosin. Real-time PCR and western blot testing were conducted to detect the gene and protein expressions of the PERK pathway-related factors GRP78, PERK, eIF2α and ATF4 in the kidney. Results Compared with the other two groups, the model group showed slow weight gain, reduced body hair gloss and inactivity. The model group had a significantly higher fasting blood glucose concentration and 24 h urinary microalbumin concentration than the control and SQW groups ( P< 0.05). Morphological observation showed the glomerular capillaries were dilated, basement membrane was irregularly thickened, mesangial area was widened, and some glomeruli had segmental sclerosis in the model group compared with the control group. Renal tubular atrophy and renal interstitial fibrous tissue proliferation were also observed in the kidneys of the model group. These pathological changes were reduced in the SQW group. Real- time PCR and western blot analysis showed that the SQW group had significantly reduced expressions of GRP78, PERK, and eIF2α compared with the model group (P<0. 05); however, the ATF4 mRNA expression did not differ between the model and SQW groups. Conclusions Diabetic renal injury in ZDF rats is alleviated by ShenQiWan, and the mechanism may be downregulation of endoplasmic reticulum stress via the PERK pathway.