Background Mesenteric panniculitis is a rare chronic fibrosing inflammatory disease that typically affects the adipose tissue and mesentery of the small intestine but may also affect the mesosigmoid and the mesocolon. The pathology of this disease remains unclear despite association with some malignancies or inflammatory disorders. We report a case of mesocolic panniculitis and a literature review of its clinical presentation, imaging findings, associated conditions and treatment options. Case presentation A 64 year-old Caucasian man was admitted to the gastroenterology department for severe weakness, left lower quadrant abdominal pain, weight loss and diarrhoea. Physical examination revealed a palpable firm mass occupying the entire left part of the abdomen. Abdominal CT-scan showed fatty infiltration of the mesosigmoid and left mesocolic fat which was strongly suggestive of panniculitis. Laparoscopic surgery revealed an inflamed and edematous mesocolon and mesosigmoid; the sigmoid mucosa appeared petechial which was suggestive of venous ischemia. Histological examination of surgical biopsies revealed mesocolic panniculitis. Despite exhaustive investigation, no associated conditions were found and the cause was classified as idiopathic. Surprisingly, the patient clinically improved without therapeutic intervention other than supportive care. Conclusion Although mesenteric panniculitis is most often a radiographic diagnosis without clinical symptomatology, it can also present with significant general status alteration. We report a case of mesocolic panniculitis complicated by development of an inflammatory mass associated with ischemic colitis. Mesenteric panniculitis is a difficult diagnosis to make which typically requires histologic confirmation. The overall prognosis is good with supportive treatment.