The effects of a novel imidazoline derivative (tizanidine) on experimental ulcers and glycoproteins in the gastric mucosa and juice of rats were examined and compared with that of clonidine. Tizanidine and clonidine inhibited indomethacin ulcer and aspirin ulcers. Tizanidine, however, did not influence stress ulcer while clonidine showed an inhibitory effect. Although tizanidine and clonidine did not increase glycoproteins in the gastric mucosa, they prevented aspirin-induced changes of glycoproteins in the gastric mucosa and juice, as well as aspirin-induced gastric ulcers. The results suggest that, as with clonidine, tizanidine inhibits drug-induced gastric ulcers and that tizanidine-mediated gastric mucosal protection may prevent gastric ulcers induced by anti-inflammatory agents.