BACKGROUND Ulcerative colitis (UC) is an autoimmune disease of unknown etiology, sometimes associated with anemia and thrombocytosis. Platelets (PLTs) play a role in amplifying inflammatory and immune responses in chronic inflammation. This study discusses the diagnosis and treatment of a case of UC combined with secondary thrombocytosis and reviews the relevant literature. We report an interaction between thrombocytosis and UC to raise clinicians' awareness of this condition. METHODS In the current report, we discuss the case of a 30-year-old female patient who presented with frequent diarrhea and thrombocytosis. METHODS Severe UC combined with intestinal infection was diagnosed based on colonoscopy and intestinal biopsy. The patient had a PLT count >450 × 109/L and was diagnosed with reactive thrombocytosis. RESULTS The patient was discharged from the hospital in remission after receiving vedolizumab and anticoagulant treatment. CONCLUSIONS In patients with severe UC with thrombocytosis, clinicians should pay attention to PLTs promoting inflammatory progression, as well as screening for venous thromboembolism risk and prophylactic anti-venous thromboembolism therapy at the time of dosing to avoid adverse effects.