The investigation of drugs used for the treatment of inflammatory diseases with limited side effects becomes an urgent need for inflammation patients. This search aimed at the preparation of novel hybrid hetero-steroids with structures especially non-ulcerogenic and anti-inflammatory activities. The heterocyclic steroids were formulated using simple and effective techniques. IR, ¹H NMR, ¹³C NMR spectra and elemental microanalysis were used to characterize the synthesized compound. The in vivo anti-inflammatory activity of some of these compounds was studied using carrageenan-induced paw oedema assay. Also, the effect of the different compounds on the development of gastric mucosal damage induced in rats by 96% EtOH administration was studied. The most marked and sustained inhibition of the oedema response was observed with the administration of the low and high doses (25 and 50 mg/kg) of compounds 8, 4, 23, 14 as well as by the high dose of compound 32. There was no significant difference in the degree of oedema inhibition between the low and high doses of compounds 8, 23, 14 at all-time points in the study. All investigated compounds administered at (50 mg/kg) dose inhibited gastric mucosal lesions induced in rats by 96% EtOH administration. Compounds 4, 9, 11, 26, 32 were the most effective in inhibiting lesion formation. No lesions were observed after the administration of compounds 9, 26 at 50 mg/kg. These findings are approaching a distinctive chance to create fresh anti-inflammatory drugs that eliminate the ulcerogenic liabilities connected with drugs presently on the market.