Microcystins (MCs) are the toxic molecules produced by common cyanobacterium in freshwater blooms. Their toxicities raise severe health issues in livestock and human beings. In current study, the immunotoxic effects of MC-LR were investigated in rabbit through evaluating the dynamics of white blood cell (WBC) numbers and cytokine production such as interleukin-3 (IL-3), IL-4, IL-6, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α). MCs at the high dose (50 μg MC-LReq kg(-1) ) significantly induced increase in the WBC number but decrease in the Th1 (IFN-γ, TNF-α) and Th2 (IL-3, IL-4, IL-6) production. In the low dose group(12.5 μg MC-LReq kg(-1) ), the number of WBC and the production of IFN-γ, IFN-α, IL-4, IL-3, and IL-6 increased gradually in first 12 h, reach the peaks at 12 h, and dropped after 24 h. Significantly positive correlations were found between the cytokines production of IL-4 and IL-6, IFN-γ and IFN-α, or IL-4 and IFN-γ. In conclusion, MC-LR is able to disturb the rabbit immune system and there exists time-dose response relationship in the MC-LR-eliciting perturbation, which probably give a better insight into investigating the immunotoxicity mechanisms of MCs in vivo. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012.