To test the hypothesis that deletion of the transient receptor potential vanilloid type 1 (TRPV1) channel exaggerates hypertension-induced renal inflammatory response, wild type (WT) or TRPV1-null mutant (TRPV1^-/-) mice were subjected to uninephrectomy and deoxycorticosterone acetate (DOCA)-salt treatment for 4 weeks. Mean arterial pressure (MAP) determined by radiotelemetry increased in DOCA-salt-treated WT or TRPV1^-/- mice, whereas there was no difference in MAP between two strains at the baseline or after DOCA-salt treatment. DOCA-salt treatment increased urinary excretion of albumin and 8-isoprostane in both WT and TRPV1^-/- mice, and the increases were greater in magnitude in the latter strain. Periodic acid-Schiff and Masson's trichrome staining showed that kidneys of DOCA-salt-treated TRPV1^-/- mice exhibited more severe glomerulosclerosis and tubulointerstitial injury compared to DOCA-salt-treated WT mice. NF-B assay showed that DOCA-salt treatment increased renal activated NF-B concentrations in TRPV1^-/- mice compared to WT mice. Immunostaining and ELISA assay revealed that DOCA-salt-treated TRPV1^-/- mice had enhanced renal infiltration of monocyte/macrophage and lymphocyte, as well as increased renal levels of proinflammatory cytokine (TNF-, IL-6) and chemokine (MCP-1) when compared to DOCA-salt-treated WT mice. Renal ICAM-1 but not VCAM-1 expression was also greater in DOCA-salt-treated TRPV1^-/- than WT mice. Dexamethasone (DEXA), an immunosuppressive drug, conveyed a reno-protective effect that was greater in DOCA-salt-treated TRPV1^-/- compared to WT mice. These data show that renal inflammation is exacerbated in DOCA-salt hypertension when TRPV1 gene is deleted and that the deterioration is ameliorated by DEXA treatment, indicating that TRPV1 may act as a potential regulator of the inflammatory process to lessen renal injury in DOCA-salt hypertension.