Background: Chronic diarrhea is a common problem in patients with symptoms related to gastro-intestinal tract. Some of these patients present with chronic non-bloody, watery diarrhea and no specific clinical, laboratory, or endoscopic findings. The aim of the present study was to investigate the value of histological findings in patients with chronic diarrhea who have normal or non-specific endoscopic findings.We also determined the frequency and distribution of histological changes related to different anatomical sites in the colon. Methods: This study was performed in Kerman city on 90 patients with chronic watery diarrhea whose diseases had not been exactly diagnosed after extensive clinical, laboratory, and endoscopic studies.Laboratory tests including complete blood count, erythrocyte sedimentation rate, C-reactive protein, stool examination, thyroid and liver function tests, and serologic study for celiac disease were all normal in this group of patients. Colonoscopy was performed and mucosal biopsies were taken from rectosigmoid, descending, and transverse colon. Results: The histologic findings were as follows: 39 (43.3%) patients showed normal histology, 25 (27.8%) patients showed microscopic colitis, not otherwise specified form. Ten (11.1%) patients had classic lymphocytic colitis, and 15 (16.7%) patients had paucicellular lymphocytic colitis. One (1.1%) patient showed focal active colitis. None of them had collagenous colitis. Conclusion: Diagnostic histological findings were seen in 28.9% of biopsy samples in patients with chronic diarrhea and normal or near normal endoscopic findings.We recommend multiple punch biopsy sampling in such patients from different sites of the colon to avoid missing some cases of microscopic colitis.