Scleroderma is a chronic autoimmune inflammatory disease with widespread fibrosis of the skin and internal organs. Scleroderma is characterized by vascular injury, immune activation, inflammation and fibrosis. However, controversies related with the pathogenesis of scleroderma are still existing. Moreover, scleroderma is the most unsuccessfully treated disease in the rheumatic disorders. Despite prominent advances in the treatments of scleroderma related renal crisis, interstitial lung fibrosis and pulmonary arterial hypertension, treatment of skin involvement still continues to be a problem. The molecular mechanism of fibrosis should be clarified for the development of new drugs and treatment.