We examined the effects of SS320A, a new cysteine derivative, on the change in the number of goblet cells induced by bacterial endotoxin in rat tracheal epithelium. Four types of goblet cell were characterized in tracheal epithelium according to their size and staining affinity with Alcian blue (AB)/periodic acid Schiff (PAS). Each rat was intratracheally given a single instillation of lipopolysaccharide (LPS) (2 mg/ml). The results showed that treatment with LPS increased the number of AB/PAS-positive cells that were recognizable as goblet cells in tracheal epithelium. On the other hand, LPS evoked acute lung inflammation related to neutrophil accumulation in the lung before the increase in goblet cells. SS320A (10-100 mg/kg, p.o.) and dexamethasone (10 mg/kg, p.o.) each significantly inhibited the increase in the number of goblet cells induced by LPS. On the other hand, ambroxol, bromhexine, l-cysteine ethyl ester and S-carboxymethylcysteine, which are used as expectorants, had no inhibitory effects on the LPS-induced change in the number of goblet cells. SS320A slightly inhibited the lung injury based on a histological examination. These data suggest that SS320A may have a beneficial effect against mucus hypersecretion in respiratory disease.