•Highly sensitive tunable mid-infrared differential absorption lidar (DIAL) for remote detection of thiodiglycol (TDG) vapor plumes is developed.•Infrared absorption spectrum of TDG is recorded using FTIR and lidar setup.•Detected the thiodiglycol vapor plumes up to a distance of about 950 m.•Daytime measurements of thiodiglycol column content varied from 10 ppm × m to 200 ppm × m. A tunable mid-infrared differential absorption lidar (DIAL) mounted on a mobile platform has been built for long range remote detection of thiodiglycol (TDG) vapor plumes. The IR spectra of TDG have been analyzed from available spectroscopy database and from the laboratory measurement. Based on the analysis, laser wavelengths at 3.190 and 3.300 μm have been selected as λon (strong absorption) and λoff (weak absorption) in the measurements. The influence of interfering molecules at these wavelengths has been also studied. The lidar return signal and sensitivity of the system have been numerically simulated based on the system parameters. The experimental DIAL system has been built using an optical parametric oscillator (OPO) based tunable laser operating in the wavelength band 3.0–3.45 μm as a transmitter and Cassegrain telescope having 200 mm diameter mirror integrated with thermoelectric cooled mercury cadmium telluride (MCT) detector as a receiver. The trans-receiver system is mounted on a pan-tilt that enables the aerial scanning operations. The lidar subsystems have been assembled and integrated on a mobile platform for conducting field experiments. An initial field testing of the system has been carried out at a remote site using the enclosed chamber containing the TDG vapor. The chamber was erected at a distance of about 950 m acted as a topographic target that reflected the laser radiation. The differential absorption signal in terms of signal ratio has been monitored continuously in real time during the trial period. The varying column content ranging from 10 to 200 ppm × m under dynamic atmospheric conditions has been calculated and discussed in this paper.