Concomitant oral supplementation of Pleurotus florida lectin (PFL) (@50μg/ml) on arsenic (@ 5 μM) exposed renal cells was investigated to evaluate the protective value of PFL against arsenic toxicity in rats. Renal cells, exposed to arsenic(III), showed a significant inhibition of cell proliferation index (CPI) and superoxide dismutase (SOD) acid and catalase (CAT) activity with an increased level of lipid peroxidation (LPO). A marginally increased level of nitric oxide (NO) was found firstly and thereafter decreased due to long-term arsenic exposure in the cells. Concurrent application of PFL in arsenic exposed renal cells had remarkable protective effect on inhibited CPI, SOD, and CAT activity and restored LPO and NO level in renal cells. Arsenic caused down-regulation of mRNA expression of SOD₂ gene that was reversed by administration of PFL. The results concluded that supplementation of PFL protected renal cells against arsenic-induced oxidative stress.