AIM: To ohserve the protective effect of chlorogenic acid on injury of cerebellar granular cells induced by amyloid β protein(Aβ) . METHODS: Cerebellar granular cells and peritoneal macrophage were cultured solely. The Aβ were added into the cultured medium and the final concentration were 10 μmol/ L for 48hours. The supernatant of macrophage were put into granular cells culture system, at same time, the chlorogenic acid were added into the culture medium and made the final concentration of chlorogenic acid to 200μmol/L, and the granular cells were continued culture for 48hous,. The levels of cytoactive, microtubule-associated protein-2(MAP-2) and leakage volume of lactate dehydrogenase(LDH) were detected with MTT, immuno-histochemical method and lactate dchydrogenase test kit. RESULTS: Supernatant of macrophage activated by Aβ moved into granular cells cultured system for 48 hours. which could decrease the cell viability of granular cells significantly to 28.35%(P< 0.01). After the chlorogenic acid were added into that medium, the cell viability were increased obviously from 28.35% to 75.82%(P<0.01). But for the group of normal granular cell with Aβ(10 μmol/ L), the granular cells only had little percent dead. After the supernatant of macrophage activated by Aβ added into the granular cells 48 hours, the MAP-2 expression of granular cells were decreased significantly compared with normal cultured granular cells, as 31.23% of normal cells. At the same time, the chlorogenic acid added into the cultured medium, the MAP-2 expression were significantly picked up (P<0.01),which get to the 79.77 percent of normal culture cells. The leakage volume of LDH increased obviously from 402 nkat/L(normal cultured granular cells) to 3046 nkat/L in the supernatant of macrophage added into normal cultured granular cells. The chlorogenic acid could reduce markedly the leakage volume of lactate dehydrogenase, which only 1285nkat/L. CONCLUSION: ① Macrophagcs could be activated by amyloid heta-protein and relcase toxic suhstance and resulted in the damage to neurons. ②The chlorogenic acid could play a role in protecting the neurons against the impairments induced by amyloid heta-protein.