In this paper, we propose a physics-inspired contrastive learning paradigm for low-light enhancement, called PIE. PIE primarily addresses three issues: (i) To resolve the problem of existing learning-based methods often training a LLE model with strict pixel-correspondence image pairs, we eliminate the need for pixel-correspondence paired training data and instead train with unpaired images. (ii) To address the disregard for negative samples and the inadequacy of their generation in existing methods, we incorporate physics-inspired contrastive learning for LLE and design the Bag of Curves (BoC) method to generate more reasonable negative samples that closely adhere to the underlying physical imaging principle. (iii) To overcome the reliance on semantic ground truths in existing methods, we propose an unsupervised regional segmentation module, ensuring regional brightness consistency while eliminating the dependency on semantic ground truths. Overall, the proposed PIE can effectively learn from unpaired positive/negative samples and smoothly realize non-semantic regional enhancement, which is clearly different from existing LLE efforts. Besides the novel architecture of PIE, we explore the gain of PIE on downstream tasks such as semantic segmentation and face detection. Training on readily available open data and extensive experiments demonstrate that our method surpasses the state-of-the-art LLE models over six independent cross-scenes datasets. PIE runs fast with reasonable GFLOPs in test time, making it easy to use on mobile devices.