This study aimed to compare the efficacy of topical dimethyl sulfoxide (DMSO), intralesional and systemic carnitine as monotherapy and in combination against ulceration in rats induced by intradermal doxorubicin extravasation. Sixty-nine 3-month-old male Wistar albino rats, weighing between 200-225 g, were used in this study. Rats were applied monotherapy or a combination of topical DMSO, intraperitoneal or intralesional carnitine. Control groups received saline or no drug. The necrotic area was measured and extravasated neutrophil leukocytes were counted in healthy tissue adjacent to necrotic areas. Monotherapy with topical and systemic carnitine did not significantly reduce the size of necrotic areas. However, topical DMSO had reduced necrotic areas and inflammatory cells significantly and the addition of systemic carnitine to topical DMSO had increased the efficacy. DMSO is an effective, safe, and easy-to-apply treatment for doxorubicin-induced extravasation. Further clinical studies are needed to evaluate the use of carnitine in combination with DMSO.