To determine whether deletion of TRPV1 exaggerates salt‐sensitive hypertension‐induced renal injury via activation of chemokine receptor 2 (CCR2), wild type (WT) and TRPV1‐null mutant (TRPV1‐/‐) mice were subjected to uninephrectomy and DOCA‐salt treatment for 4 weeks with or without selective CCR2 antagonist, RS504393. DOCA‐salt treatment increased systolic blood pressure (SBP), urinary excretion of albumin and 8‐isoprostane, and decreased creatinine clearance compared with the control. DOCA‐salt treatment also caused obvious glomerulosclerosis, tubulointerstitial injury and monocyte/macrophage infiltration compared with the control. The changes in the parameters were greater in TRPV1‐/‐ mice compared with WT mice with the exception of SBP. Blockade of the CCR2 with RS504393 (4 mg/kg) had no effect on SBP. However, treatment with RS504393 prevented renal functional and morphological damage, and reduced the increase in monocyte/macrophage infiltration in DOCA‐salt hypertensive WT and TRPV1‐/‐ mice with the greater in the latter. Our results suggest that TRPV1 attenuates salt‐sensitive hypertension‐induced renal damage possibly via suppression of CCR2. (This work was supported by grants from the National Natural Science Foundation of China (No. 81170243) and Henan Provincial Science and Technology Innovative Program for Outstanding Scholarship (No. 124200510007).Grant Funding Source: NNSF of China (No. 81170243), Henan Provincial STlPOS(No.124200510007).