Objective To observe the effect of Ningshen Qushi Huayu decoction on the expressions of angiotensin II type 1 receptor(AT1R), hypoxia inducible factor 1α(HIF-1α) and heme oxygenase-1(HO-1) in lupus nephritis mice. Methods Lupus nephritis mice model were induced by chronic graft-versus-host disease(cGVHD). The mice were divided into blank group, model group and low, medium and high dose groups of Ningshen Qushi Huayu decoction. In the blank group, there was no model making and normal saline intervention. In the model group, normal saline intervention. In the low, middle and high dose groups, Ningshen Qushi Huayu decoction were administered by gavage at the concentrations of 19.5, 39 and 78 g/kg, respectively. After 8 weeks of intervention, mice were executed and their kidneys were taken under aseptic conditions. The gene expressions of AT1R, HIF-1α and HO-1 in kidney tissues were detected by qPCR. Results The incidence of proteinuria was 0% in the blank group and 50% in the saline group (model group in seven weeks. HE staining of liver, kidney and intestine showed that inflammatory cells infiltrated significantly in the model group. ELISA showed that the contents of IgG, IgG1 and IgG2 in serum increased significantly(P<0.05), suggesting that the model of lupus nephritis was successful in mice. Compared with the blank group, the expressions of AT1R, HIF-1a and HO-1 in saline group increased(P<0.05). Compared with model group, the expressions of AT1R, HIF-1a and HO-1 in low, middle and high dose groups of Ningshen Qushi Huayu decoction were decreased(P<0.05), and there was a dose depend trend. Conclusion Ningshen Qushi Huayu decoction can improve the symptoms of lupus nephritis mouse model, and its mechanism may be related to the decreased expressions of AT1R, HIF-1α, and HO-1 genes in kidney.