Abstract Disclosure: K.N. Islam: None. R.K. Islam: None. M.B. Rashid: None. B. Smith: None. Diabetes is a leading cause of morbidity and mortality. Elevation of oxidative stress is a common cause in diabetic patients because of higher levels of blood sugar concentration. Nitric oxide (NO) is a gasotransmitter that has many health benefits for many disease conditions. NO also has an antioxidant property. The pancreatic β-cells are insulin-secreting cells. The present study was undertaken to investigate the effects of NaNO2, a donor of NO on glucose-induced oxidative stress in pancreatic β-cells (HIT) from a Chinese hamster. First, we determined the effects of dose responses of glucose (25, 50, 75, 100, and 150 mM) on the induction of oxidative stress as it was measured by the formation of thiobarbituric acid reactive substances (TBARS) in serum starved β-cells. We observed marked oxidative stress in the serum starved β-cells by the treatment with 75 mM of glucose. Later, we tested the effects of NaNO2 on glucose-induced oxidative stress in serum starved β-cells, and we found that NaNO2 markedly inhibited glucose-induced oxidative stress in serum starved β -cells. Treatment with NaNO2 caused significant induction of cell viability and a marked reduction of cellular cytotoxicity in β-cells under serum starvation incubated without or with glucose. In addition, NaNO2 treatment of β-cells antagonized expression levels of inflammatory cytokines, TNF-α and inhibited the activation of the transcription factor, NF-κB signaling pathway. Our findings suggest that NO or NO donors may be used as therapy to cure diabetes via inhibiting oxidative stress thereby decreasing blood sugar levels in diabetic patients. Presentation: 6/3/2024