Patients with various malignancies can develop malignant pleural effusion (MPE). MPE is the abnormal accumulation of fluid in the pleural cavity. This fluid usually contains immune cells, tumor cells, and high levels of plasma proteins. This condition is associated with impaired pleural fluid drainage and is considered an immune and angiogenic manifestation of tumors metastasized in the pleura from other thoracic and non-thoracic areas. Tumor-induced pleural vascular hyperpermeability and neoangiogenesis are crucial to pleural fluid accumulation and could be therapeutically targeted to minimize MPE development. Here, we present two methodologies required for assessing the angiogenic properties of MPE fluid—Evans’ blue pulse-and-chase for evaluating increased vascular permeability and the chorioallantoic membrane (CAM) assay to assess tumor-triggered angiogenesis. We describe the steps for experimental MPE formation in mice, including MPE fluid collection, evaluation of MPE-induced vascular permeability, and assessment of MPE-induced angiogenesis.