Abstract: To explore the correlation between aquaporin protein ( AQP1 ) and malignant pleural effusion as well as to provide scientific basis for related clinical treatment. Methods: The mechanisms of malignant pleural effusion were discussed, and the expression levels of AQP1, CD34, and TNF-α were determined using immunohistochemistry and fluorescent quantitation real-time polymerase chain reaction ( PCR ). Results: Immunostaining results revealed the high expression of AQP1 in the microvascular endothelia near the visceral pleura and a weak expression in the mesothelial cells in the visceral pleura. Quantitative PCR results showed that CD34 and TNF-α expression in the pleural effusion of cancer tissue significantly increased compared with the control group, and there were no spilled cancer tissue and inflammatory effusion ( P < 0.05 ). CD34 expression is closely associated with VEGF, but not correlated with AQP1 expression. This condition implies that the reduced expression of AQP1 under a cancer pathophysiological condition is associated with pleural effusion. Conclusion: High CD34 expression in the cancer tissue of non-small cell lung cancer with pleural effusion results in increased angiogenesis. High TNF-α expression can increase vascular permeability. These two mechanisms cause an increment in the pleural effusion, resulting in an increase of new blood vessels without a synchronous increase in AQP1. The latter  finally disrupts the balance of water in the thorax and develops malignant pleural effusion. Further studies are needed to elucidate the potential pathophysiological role of AQP1 in malignant pleural effusion.