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We have applied a flat-panel detector to an X-ray cone-beam micro computed tomography (micro-CT) for small-animal imaging. The flat-panel detector consists of an active matrix of transistors and photodiodes with a pixel pitch of 50 μm and a thallium-doped cesium iodide (CsI:Tl) scintillator as an X-ray-to-light conversion layer. The detector was fabricated with a complementary metal-oxide-semiconductor (CMOS) technology capable of a submicrometer design line width, hence, it has a pixel fill-factor as high as ∼80%. In addition, the detector has a very fast response characteristic with an image lag less than 0.3% in the frame integration time of 5 s. The CMOS flat-panel detector has been tested in terms of modulation transfer function, noise power spectrum, and detective quantum efficiency. Tomographic imaging performances of the micro-CT system, such as voxel noise, contrast-to-noise ratio, and spatial resolution, have also been evaluated by using various quantitative phantoms. Experimental results of euthanized laboratory rat imaging suggest that the micro-CT system employing a CMOS flat-panel detector can be greatly used in small-animal imaging.