Objective To establish a rat model of Cryptococcus neoformans meningitis. Methods Sprague-Dawley rats were divided into four groups (group A to D). The load of Cryptococcus neoformans was inoculated by intracisternal injection to the animals in Group A (1×105 cfu), Group B (1×106 cfu), Group C (1×107 cfu), and 0.9％ NaCl solution to Group D. The rats were observed after inoculation for their clinical symptoms. On day 14 and day 21 after inoculation, cerebrospinal fluid was sampled and cultured for counting of bacterial colonies. The 28-day mortality of the animals was calculated. Results All the animals in group A (1×105 cfu) survived without any apparent clinical symptoms, and associated with decreasing bacteria load. The animals in group B (1×106 cfu) had mild symptoms associated with low mortality rate and slightly increased bacterial load. The animals in group C (1×107 cfu) showed a lot of symptoms and associated with high mortality rate and significantly increased bacteria load. All the animals in group D (0.9％ NaCl solution) survived with normal activity. No bacterial colony was cultured from the cerebrospinal fluid. Conclusions Intracisternal injection of 1×107 cfu Cryptococcus neoformans to rats could cause apparent clinical symptoms of meningitis. The 28-day mortality rate of such a rat model of Cryptococcus neoformans meningitis is greater than 80％. An ideal rat model of Cryptococcus neoformans meningitis is established successfully.