Nicolau syndrome is a rare adverse reaction at the site of an intramuscular injection, and is characterized by severe pain immediately after the injection and rapid development of distinct skin lesions. As this syndrome is rare, it may be overlooked at the early clinical phase and subsequently, clinical outcomes may be worse due to delay in treatment. We report on a female who developed Nicolau syndrome following intramuscular diclofenac injection, which required surgical reconstruction. Understanding the characteristics of Nicolau syndrome and careful surveillance for relevant clinical features may help physicians to more quickly diagnose and treat this condition.