Angiogenesis plays an important role in tumor growth and expansion, which makes it one of the most critical subjects in oncologic research. Angiogenesis can be imaged with photoacoustic microscopy (PAM), however the lateral resolution deteriorates significantly out of focus. Virtual-point-detector-based synthetic aperture focusing technique (SAFT) combined with the coherence weighting factor (CF) can alleviate the blurring, at a cost of anisotropy of resolution. In this study, a two-dimensional SAFT with CF was investigated to improve resolution and yield lateral resolution isotropy simultaneously. In a phantom study, two carbon fibers with a diameter of 6 mu m fixed perpendicularly to each other were imaged with PAM developed in our laboratory. In the depth range of 0.6 mm near the focal spot, the best resolution processed with one-dimensional (ID) SAFT is 40 mu m better than that processed with two-dimensional (2D) SAFT. However, the maximum difference in lateral resolution between the z-x and z-y planes is about 15 mu m processed with 2D SAFT, while it is 145 mu m processed with ID SAFT. Furthermore, the 2D SAFT increased the signal-to-noise ratio (SNR) by up to 8 dB higher than ID SAFT at an imaging depth of 700 mu m below the focal spot. Finally, in vivo imaging of the dorsal subcutaneous microvasculature of a mouse was used to validate the improved performance of 2D SAFT. (C) 2011 American Institute of Physics. [doi :10.1063/1.3585828]