Abstract: Based on the published and recent measurement of microcystins (MCs) in Lake Taihu from 1999 to 2021, the long-term variation and health risks of MCs were analyzed by Mann-Kendall trend test and hazard quotient index to provide support for further strengthening of MCs monitoring and risk assessment. The results showed that the total MC (TMC), intracellular MC (TIMC) and extracellular soluble MC (TEMC) concentrations have been increasing slowly since 1999, and the monthly mean concentrations of TMC and TEMC ranged from 0.01-19.50 μg/L and 0.001-6.44 μg/L, respectively. For seasonal variation, the three kinds of MC in spring showed an upward trend year by year, while summer and autumnTEMC showed an upward trend in winter. In different lake areas, TMC and TIMC also showed an increasing trend, especially in the central and southern lake area, and the Eastern Lake. The TEMC concentration increased in Gonghu Bay, and the average annual TEMC concentration was the highest in Zhushan Bay (0.53 μg/L), the TEMC concentration was the highest in Meiliang Bay in summer and autumn. Health risk assessment showed that there were three TEMC exposure risk peaks in Lake Taihu, and the risk value was the highest during 2013-2015. The risk value of TEMC in Zhushan Bay was the highest, followed by Meiliang Bay. This study can provide the scientific basis for health risk assessment and control of harmful cyanobacterial blooms in shallow lakes.