Background: Acute pancreatitis (AP) is a global inflammatory disease with high morbidity and mortality rates. Nifedipine, an antioxidant and anti-inflammatory, can prevent oxidative stress-induced acinar cell damage. Aim of the work: The study aimed to investigate the possible protective effect of Nifedipine against L-arginine induced AP in adult male albino rats. Materials and methods: The study involved 40 adult male albino rats in five groups (n=8, each group): normal control, Nifedipine (5mg/Kg/day/orally for one week), AP induced in the other groups by 2 doses of L-arginine Hcl injections (250mg/100gm) with 1 hour interval between the two doses, then divided in to  L-arginine group (AP), L-arginine + Nifedipine for 1 week, and recovery group which is L-arginine group left for 2weeks. After sacrifice, rats' pancreas were examined for biochemical, histological, immuno-histochemical, and morphometric studies. Results: The study revealed distortion & irregular acinar architecture, dilated and congested blood capillaries, inflammatory cell infiltration, cytoplasmic vacuolations and widened spaces CT stroma between the pancreatic lobules and around the acini. The islets appeared atrophied. The L-arginine + Nifedipine group showed improvement in histological architecture. Nifedipine attenuated AP by decreasing serum amylase and lipase levels, oxidative stress stimulation, and pancreatic tissue levels of MDA, MPO, and TNF-α. It also increased GSH and Nrf2 content in addition to a significant decrease in immunoreactivity of Caspase-3 & NF-kB. The recovery group showed mild improvement in some histological and biochemical findings. Conclusion: Nifedipine is recommended as an adjuvant treatment due to its strong therapeutic effects during acute pancreatitis course treatment.