Rationale: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.Patient concerns:In the current report, we discuss the case of a 30-year-old female patient who presented with frequent diarrhea and thrombocytosis.Diagnosis: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.Interventions and outcomes:The patient was discharged from the hospital in remission after receiving vedolizumab and anticoagulant treatment.Lessons: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.