For biomedical microanalysis systems requiring implementation of optical signal generation and detection, we propose a package of VHDL-AMS functions to allow co-simulations of optical path, opto-electronic elements and associated electronics. This package contains a set of functions, which may be used for functional description of parts of microanalysis systems. An overview of simulation techniques shows that VHDL-AMS allows continuous-time simulation of polychromatic optical signals needed by the wavelength shifting nature of fluorescence. Indeed, directivity of optic path is well managed by VHDL-AMS using directional ports. By design, optical signals are easily simulated together with associated command and processing electronic circuits. Inspired by RF simulation techniques, the proposed description of polychromatic optical signals lies on a discretization of spectra. This format allows each optic band to be processed independently by models. The array data structure available in VHDL-AMS provides a compact form to device descriptions and to optical signal connexions. Fluorescence is modelled with absorbance and emission spectra, and optical couplings are described using results of geometric-optic analysis. A “spectral plug-in” has been developed, to be connected to output-power models of LASER-LED reported in the literature. Furthermore, a physical model of the CMOS Buried Double Junction (BDJ) detector has been described. Models of optic and electronic parts include a modulated LASER source, fibre optic, fluorochrom, BDJ detector and Constant Voltage Threshold (CVT) analogue-to-digital signal conversion. The system-level simulations, with Variable-Time Synchronous Detection (VTSD) are performed using the “Advanced-MS” environment. The validity domain of this approach as well as limitations of the available VHDL-AMS simulators (especially in terms of convergence and simulation time) are discussed.