The role of gastrin in regulating the transport of water and electrolytes through the colonic epithelium is unclear. The aim of this study was to examine the effect of omeprazole on gastrin levels and morpholigical features of the colonic mucosa. Methods: In adult male Wistar rats under urethane anesthesia a colonic loop was isolated and perfused in vivo for determining net water and electrolyte (Na⁺, K⁺, Cl^- ) movements (Jnet). Group 1 (baseline, n=20) received a vehicle i.p. for 1, 2, 3 and 4 weeks. Groups 2-5 (n=27) received omeprazole (Dr.Reddy's, India, 14 mg/kg, i. p.) for 1–4 weeks. Plasma gastrin level was determined by radioimmunoassay. Morphometrically, mucosal thickness, crypt depth, and nuclear profound area were measured. Results: After 1 week, gastrin levels were 207% higher and NaCl absorption lower than baseline. After 2 weeks, no significant morphometric changes were observed. After 3 weeks, gastrin levels were 131% of baseline levels. Crypt depth and mucosa thickness had increased, while JnetNa⁺ had decreased. After 4 weeks, gastrin levels were 189% of baseline levels. Nuclear profound area was smaller, crypt depth and mucosa thickness were greater than baseline. Conclusions: The short-term omeprazole-induced HG alters the electroneutral absorption of NaCl. The prolongation of HG up to 3 weeks displays the first manifestation of the trophic effect of gastrin along with altered electrogenic JnetNa⁺ absorption.