Abstract : In this paper, we present a new fully automatic approach for noise parameter estimation in the context of fluorescence imaging systems. In particular, we address the problem of Poisson-Gaussian noise modeling in the nonstationary case. In microscopy practice, the nonstationarity is due to the photobleaching effect. The proposed method consists of an adequate moment based initialization followed by Expectation-Maximization iterations. This approach is shown to provide reliable estimates of the mean and the variance of the Gaussian noise and of the scale parameter of Poisson noise, as well as of the photobleaching rates. The algorithm performance is demonstrated on both synthetic and real fluorescence microscopy image sequences.