Background: Acute pancreatitis (AP) is a life-threatening inflammatory disease. Apremilast (Otezla) is an orally active small drug that inhibits phosphodiesterase-4 (PDE4) & modulate the inflammatory mediators. NO researches were done to detect its role in treatment of AP. Aim: this study was aimed to determine the role of apremilast on AP produced by L-arginine. Materials & methods: A rat model of AP was developed using two intraperitoneal (IP) injections of L-arginine 250 mg/kg body weight, separated by a one-hour period. The treatment group received apremilast at a single daily oral dosage of 20mg/kg body weight for five consecutive days after IP injections of L-arginine at the same dose as before. By the end of the experiment, blood sample were obtained for estimation of oxidative stress parameters malondialdehyde [MDA], glutathione [GSH], then rats were sacrificed. The pancreas of all treated animals were excised, prepared for estimation of tumour necrotic factor (TNF- alpha) & interleukin-10 (IL-10) in tissues and histopathological examination. Results: Rats with AP had histological alterations consistent with pancreatic tissue damage, as well as elevated blood glucose, serum amylase, and lipase enzyme activities. Additionally, AP rats had elevated levels of the pancreatic inflammatory biomarker TNF-alpha and reduced levels of the anti-inflammatory biomarker IL-10. Additionally, the oxidative stress biomarker MDA was elevated in AP, whereas the antioxidant GSH level was reduced as compared to control group. Co-administration of Aprimelast resulted in substantial improvements in both pre-existing parameters and histology. Conclusion: These results suggested that apremilast may have beneficial therapeutic effect on L- a rginine induced AP in adult albino rats owing to its anti-inflammatory and antioxidant properties.