The regularization of retinal oxygen tension estimation was previously proposed with an assumption that phosphorescence intensity images are corrupted by additive Gaussian noise. Based on this assumption, a regularized least-squares estimate has been shown to be better than a conventional least-squares estimation. However, this assumption is inconsistent with the acquisition process of phosphorescence intensity images acquired using an intensified charge-coupled device camera. Almost the entire acquisition process is governed by the natural aspects of photons. Therefore, a method based on photon counting statistics is more appropriate. In this study, we propose a regularized oxygen tension estimation method based on photon counting statistics and a phosphorescence lifetime imaging model.