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Rate control plays an important role in video coding. However, in the conventional rate control algorithms, the number and position of macroblocks (MBs) inside one basic unit for rate control is inflexible and predetermined. The different characteristics of the MBs are not fully considered. Also, there is no overall optimization of the coding of basic units. This paper proposes a new region-based rate control scheme for H.264/advanced video coding to improve the coding efficiency. The inter-frame information is explored to objectively divide one frame into multiple regions based on their rate-distortion (R-D) behaviors. The MBs with similar characteristics are classified into the same region, and the entire region, instead of a single MB or a group of contiguous MBs, is treated as a basic unit for rate control. A linear rate-quantization stepsize model and a linear distortion-quantization stepsize model are proposed to accurately describe the R-D characteristics for the region-based basic units. Moreover, based on the above linear models, an overall optimization model is proposed to obtain suitable quantization parameters for the region-based basic units. Experimental results demonstrate that the proposed region-based rate control approach can achieve both better subjective and objective quality by performing the rate control adaptively with the content, compared to the conventional rate control approaches.