The aim of this study was to assess the renoprotective effect of renal human liver-type fatty acid binding protein (hL-FABP) and angiotensin II (Ang II) type 1a receptor (AT1a) loss in renal injury caused by renin-angiotensin system (RAS) activation. We established hL-FABP chromosomal transgenic mice (L-FABP^+/-AT1a^+/+), crossed the L-FABP^+/-AT1a^+/+ with AT1a knock-down homo mice (L-FABP^-/-AT1a^-/-), generated L-FABP^+/-AT1a hetero mice (L-FABP^+/-AT1a^+/-). After the back-cross of these cubs, L-FABP^+/-AT1a^-/- were obtained. In order to activate the renal RAS, wild type mice (L-FABP^-/-AT1a^+/+), L-FABP^+/-AT1a^+/+, L-FABP^-/-AT1a^+/-, L-FABP^+/- AT1a^+/-, L-FABP^-/-AT1a^-/- , and L-FABP^+/-AT1a^-/- were administered high dose systemic Ang II infusion plus a high salt diet for 28 days. In the L-FABP^-/-AT1a^+/+, RAS activation (L-FABP^-/-AT1a^+/+RAS) caused hypertension and tubulointerstitial damage. In the L-FABP^+/-AT1a^+/+RAS, tubulointerstitial damage was significantly attenuated compared with L-FABP^-/-AT1a^+/+RAS. In the AT1a partial knockout (AT1a^+/-) or complete knockout (AT1a^-/-) mice, reduction of AT1a expression led to a significantly lower degree of renal injury compared with L-FABP^-/-AT1a^+/+RAS or L-FABP^+/-AT1a^+/+RAS mice. Renal injury in L-FABP^+/-AT1a^+/-RAS mice was significantly attenuated compared with L-FABP^-/-AT1a^+/-RAS mice. In both L-FABP^-/-AT1a^-/-RAS and L-FABP^+/-AT1a^-/-RAS mice, renal damage was rarely found. The degrees of renal hL-FABP expression and urinary hL-FABP levels increased by RAS activation and gradually decreased along with reduction of AT1a expression levels. In conclusion, in this mouse model, renal hL-FABP expression and a decrease in AT1a expression attenuated tubulointerstitial damage due to RAS activation.