Self-training has greatly facilitated domain adaptive semantic segmentation, which iteratively generates pseudo labels on the target domain and retrains the network. However, since the realistic segmentation datasets are highly imbalanced, target pseudo labels are typically biased to the majority classes and basically noisy, leading to an errorprone and sub-optimal model. To address this issue, we propose a region-based active learning approach for semantic segmentation under a domain shift, aiming to automatically query a small partition of image regions to be labeled while maximizing segmentation performance. Our algorithm, Active Learning via Region Impurity and Prediction Uncertainty (AL-RIPU), introduces a novel acquisition strategy characterizing the spatial adjacency of image regions along with the prediction confidence. We show that the proposed region-based selection strategy makes more efficient use of a limited budget than image-based or pointbased counterparts. Meanwhile, we enforce local prediction consistency between a pixel and its nearest neighbor on a source image. Further, we develop a negative learning loss to enhance the discriminative representation learning on the target domain. Extensive experiments demonstrate that our method only requires very few annotations to almost reach the supervised performance and substantially outperforms state-of-the-art methods.* Corresponding author (a) Target image (b) Image-based selection (100%) (c) Point-based selection (2.2%) (d) Region-based selection (2.2%)