OBJECTIVE: To investigate the effects of water extract from Poria cocos on the mitochondria impairment of primary cultured hippocampal neurons induced by sodium azide. METHODS: The hippocampal neurons from newborn rats were primarily cultured for 11 days. After the culture media was disposed, the neurons were incubated with MTT (0.4 mg·mL -1 ) for 4 h. The cell viability was judged by the percentage of MTT reduction which was measured by the enzyme immunity autoanalysor at the wavelength of 550 nm. The change of cytoskeleton labeled with (α-tubulin antibody) was observed by laser scanning confocal microscopy. RESULTS: Sodium azide injured hippocampal neurons dose-dependently. The cytoskeleton was significantly damaged when the hippocampal neurons were incubated with sodium azide at the dose of 64 mmol·L -1 . The microtubule of neurons became disorder and blur, and the percentage of MTT reduction of the mitochondria in the neurons was (60.73 ±5.13) % compared with the control. However, after being incubated with neurons, the water extract from Poria cocos ( 10 ∼ 20 mg·mL -1 ) showed a significantly protective effect against the MTT reduction decrease in neurons induced by sodium azide. Furthermore, the intact structure of microtubule was seen clearly in primary cultured neurons. CONCLUSION: Poria cocos was demonstrated to play an important role in maintaining the function of mitochondria and normal morphology of neurons.