Objective This study was designed to determine the effect of transient receptor potential vanilloid type 4 (TRPV4) on angiotensin II (Ang II)-induced renal injury in TRPV4-null mutant (TRPV4 ^{- / -} ) mice. Methods The mice were divided into sham group and Ang II-treated group. Ang II was infused systemically into wild type (WT) and TRPV4 ^{- / -} mice via a miniosmotic pump for 4 weeks, and the sham mice were given with normal saline. Systolic blood pressure, urinary excretion of albumin and 8-isoprostane, serum creatinine, and the pathological changes in the kidney tissues were assayed after the 4-week treatment. Results Compared with corresponding sham mice, Ang II infusion led to enhanced systolic blood pressure, increased urinary excretion of albumin and 8-isoprostane, increased serum creatinine (P< 0.05), and enhanced glomerulosclerosis degree and renal tubulointerstitial injury index (P < 0.05) in the WT and TRPV4 ^{- / -} mice. The result were associated with enhanced collagen levels in the kidney (P < 0.05). All of them were attenuated by the deletion of TRPV4 in the absence of alteration in blood pressure (P < 0.05). Conclusions Deletion of TRPV4 could alleviate renal injury during Ang II-induced hypertension, suggesting that TRPV4 may contribute to the pathophysiology of angiotensin II-induced renal injury.