AbstractObjective: Preclinical characterization of methylprednisolone aceponate.Results: The local antiinflammatory potency of methylprednisolone aceponate was equal to the very strong glucocorticoid clobetasol 17‐propionate but higher than the potency of hydrocortisone 17‐butyrate after topical application in 2 animal models of inflammation. Methylprednisolone aceponate is activated enzymatically in the skin. This activation proceeds faster in inflamed tissue. In contrast to clobetasol 17‐propionate, methylprednisolone aceponate was devoid of systemic effects after topical application for 3 days. Finally, whereas clobetasol 17‐propionate induced marked skin atrophy, methylprednisolone aceponate induced only slight atrophogenic changes after long‐term application (up to 43 days) on rat skin, comparable to the effects of hydrocortisone 17‐butyrate.Conclusions: Methylprednisolone aceponate combines high local antiinflammatory potency with very low systemic side effects and only minor local atrophogenic activity. The reason for the dissociation between local antiinflammatory and atrophogenic effects is not known so far. It may be speculated that one of the reasons for the very strong local antiinflammatory activity may reside in the faster enzymatic activation in inflamed tissue. Methylprednisolone aceponate represents a new corticosteroid with which it is possible to improve the dissociation between desired antiinflammatory activity and undesired side effects of topical gluc