Background: Pyoderma gangrenosum (PG) (ulcerating neutrophilic dermatosis) is a rare disease that about of half of these patients have a systemic disorder, particularly Crohn's and ulcerative colitis. In addition, inflammatory lesions play key role in its pathogenesis. In early diagnosis of disease, we will further prevent of serious consequences of the disease. In this report, a case of PG after the vaginal surgery with history of ulcerative colitis was introduced. Case presentation: A 37-years old woman was admitted in an University Hospital of Mashhad University of Medical Sciences, Iran, in 2016 two weeks after genital surgery. The chief complaints were fever, painful tenderness, ulcerative lesion and inflammatory papule on surgical site and thigh. She suffered of fever despite received oral and then wide spectrum intravenous antibiotic therapy. Blood cultures and wound culture were negative. In addition to two deferent intravenous antibiotics, topical wound debridement was performed. Despite this course of treatment which did not improve the lesion, biopsy was performed. Histopathology features of biopsy specimen indicated prominent neutrophils mixed inflammation and lymphocytic vasculitis indicated as pyoderma gangrenous. The patient's medical history included associated ulcerative colitis from 18 years ago and she was under irregular oral receiving of Asacol (mesalamine). Intravenous corticosteroid therapy was administered which led to response of skin of right thigh and surgical site inflammation. After 6-months follow-up, the patient is still in good condition. Conclusion: Based on major variable clinical manifestations and no diagnostic serologic test of pyoderma gangrenosum, diagnosis of this disease is difficult. Increased awareness about PG and exclusion of other etiologies such as inflammatory and immunologic disease will aid in prompting of pyoderma gangrenosum diagnosis and proper management of the disease.