OK-432 therapy is effective for the treatment of macrocystic lymphatic malformations (LMs), but the optimal management of patients with microcystic LMs associated with large chylous pleural effusions or chylous ascites is not resolved. We performed thoracoscopic- or laparoscopic-guided injection of OK-432 for 2 patients with diffuse microcystic LMs accompanied by refractory chylous pleural effusion or chylous ascites. Both cases responded well to OK-432 therapy with improvement/resolution of fluid collections and associated symptoms. We recommend the use of OK-432 therapy as a promising treatment for microcystic LMs with functionally significant lymphatic fluid collections.