This laboratory has recently reported the solubility and in vivo absorption enhancement of diclofenac sodium by β-cyclodextrin complexation. The acute gastroduodenal mucosa injury provoked by administration of 34 ㎎/㎏ and 68 ㎎/㎏ of a diclofenac sodium (DS) and equivalent dose of new formulation [diclofenac sodium-beta-cyclodextrin complexation(DS-β-CD)] was evaluated and compared. Microscopic examinations, performed after 18-hrs treatment, demonstrated that DS-β-CD was less gastrolesive than DS. The drop in gastrophy after a single dose of the assigned drug was considerably greater for DS than for DS-β-CD, which registered similar values to control. Since gastrophy is an expression of the anatomy-functional integrity of the gastric barrier, the results indicate that DS-β-CD exerts less direct acute damage on the gastric mucosa. Therefore, when administered short-term, DS-β-CD appears to be less gastrolesive than the standard DS formulation.