The current study was carried out to evaluate the antioxidant and anti-caspase 3 activity of chitosan-
Pinus merkusii
nanoparticle in against lead acetate-induced nephrotoxicity in rats. chitosan-
P. merkusii
nanoparticle was characterized by dynamic light scattering (DLS) and scanning electron microscope (SEM). The male rats were divided into control group (rats were given with distilled water), lead acetate group (rats were injected with lead acetate 15 mg/kg BW i. p), and the treatment group (rats were given the chitosan-
P. merkusii
nanoparticle 150 mg, 300 mg, 600 mg/kg BW orally and were injected with lead acetate 15 mg/kg BW). The rats blood samples were measured levels of blood urea nitrogen (BUN) and creatinine. The kidney tissues were collected to evaluate the malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx). Histological to evaluate renal damage, and immunohistochemical to analyze the expression of caspase 3. The results showed that DLS showed the size of chitosan-
P. merkusii
nanoparticle was 165.9 ± 24.18 nm. SEM images of the chitosan-
P. merkusii
nanoparticles showed an irregular shape and its the rough surface. Administration of lead acetate resulted in a significant increase in levels of the BUN, creatinine, MDA level, caspase 3 expression, and a decrease in SOD and GPx were compared with the control group. Treatment with the chitosan-
P. merkusii
nanoparticle 600 mg/kg BW significantly decreased the elevated BUN, creatinine, MDA levels, caspase 3 expression and also increase in SOD and GPx as compared to lead acetate group. The lead acetate induced loss of the normal structure of renal cells and necrosis, whereas treated with chitosan-
P. merkusii
nanoparticle improved renal cell necrosis. This study indicates that chitosan-
P. merkusii
nanoparticles appeared to be a promising agent for protection against lead-induced nephrotoxicity through increasing antioxidant and inhibiting caspase 3 expression.