The current study characterized pleural changes induced by talc pleurodesis (TP), based on serial positron emission tomography/computer-tomography (PET/CT) with F-18 fluorodeoxyglucose (FDG). A total of 8 cancer patients who had both TP and PET/CT and no evidence of active pleural involvement after TP were retrospectively evaluated. Maximum standard uptake values, maximum Hounsfield units (HU), and thickness were followed over time. The 8 patients had 25 PET/CT scans performed in an average of 22 months after TP. An increased FDG uptake was associated with an increase in pleural thickness within 5 months after TP, and both parameters showed statistical significance as compared with findings before TP. After 5 months of TP, the standard uptake value appeared to persist or increase further, and the pleural thickening stabilized. The formation of calcification was a slow process and might lag behind the changes in FDG metabolism and pleural thickness. The HU did not change significantly once pleural calcification had been formed. Knowledge of aforementioned pleural changes may help differentiate TP induced pleural inflammation from pleural malignancy and to avoid false-positive interpretation of FDG PET/CT exams.