Fifteen cats with eosinophilic granuloma or eosinophilic plaque were given PLR 120 at the dosage of 10 mg kg−1 twice daily for one month. PLR‐120 down‐modulates mast cell degranulation via a receptor‐mediated mechanism. No other drugs were permitted and cats were kept free of parasites throughout the study. A clinical evaluation and skin biopsies were performed before and after the treatment. Clinical improvement was assessed at 15 and 30 days. Mast cell numbers were counted and their granular content was assessed by densitometric analysis on toluidine blue‐stained sections before and after the treatment. Ten of 15 (67%) cats showed clinical improvement of signs and lesions. There was no significant difference between mast cell numbers in skin biopsies taken before and after the trial, whereas the number of granules was significantly increased (P < 0.009). This pilot study suggests that PLR‐120 might be a useful drug for the treatment of eosinophilic granuloma and eosinophilic plaque.