A new theoretical approach for photoacoustic (PA) image simulation of an ensemble of cells with endocytosed gold nanoparticles is presented. Each cell was approximated as a fluid sphere and suspended in a nonabsorbing fluid medium. It was assumed that the cellular optical absorption coefficient changed greatly because of endocytosis of nanoparticles; however, thermophysical parameters remained unchanged because nanoparticles occupied negligible intracellular volume. A frequency-domain method was used to obtain a PA signal from a single cell and resultant signal detected by a focused single-element transducer was evaluated by convolving signals from many cells with the spatial impulse response function of the receiver. The proposed model was explored to simulate PA images of numerical phantoms. It was observed that features of the phantoms are retained precisely in those simulated images. Also, speckles in PA images are significantly suppressed because of strong boundary buildup when cells are bounded to a region. Nevertheless, speckle visibility increases when cells are not bounded to a region. This approach may be developed as a realistic simulation tool for PA imaging of tissue medium utilizing its cellular feature.