Two novel series of oxadiazole and oxadiazoline analogs possessing an indole nucleus were synthesized for their potential anti-inflammatory activity. The structures of the compounds were elucidated by elemental and spectral (IR, (1)H-NMR, (13)C-NMR, and MS) analysis. Most of the test compounds demonstrated appreciable anti-inflammatory activities. The anti-inflammatory activity of oxadiazoles at doses of 100 mg/kg was shown by their ability to provide 27-66%, 14-32%, and 20-51%. protection against carrageenan-induced rat paw edema, moist cotton pellet-induced, and dry cotton pellet-induced granuloma, respectively. On the other hand, the anti-inflammatory properties of oxadiazolines at doses of 100 mg/kg were reflected by their ability to provide 20-56%, 11-26%, and 25-47% protection against carrageenan-induced rat paw edema, moist cotton pellet-induced, and dry cotton pellet-induced granuloma, respectively. The ulcerogenic potential of the compounds was determined. Structure-activity relationships among synthesized compounds were also established.