Micro/nano-fabrication of polymers and micro-processing of real human tissues via plasma-mediated ablation were investigated using an ultra-short pulsed (USP) laser of 900 fs pulse duration and 1552 nm center wavelength. For the PDMS polymer micro-fabrication, the ablation threshold for the single spot and the single line scanning ablation features were studied at first. The single pulse ablation threshold is determined to be 4.62 J/cm ² and the incubation factor for the multi-pulse ablation is found to be 0.52. The influences of pulse overlap rate and irradiation pulse energy on the ablation line width, internal ablation interface depth, and ablation surface quality were scrutinized. Then the thin layer PDMS separation was completed with thickness controllable via adjusting the laser focus spot position. For the three tests with a target thickness of 20 μm, the averaged thickness of the separated thin layers is 20.6± 1.7 μm. And a multi-width micro-channel interconnected network was fabricated and the size of the channels varies from 50 to 400 μm. For the real tissue ablation, the fundamental ablation features were investigated. It is found that the threshold of the single pulse ablation for the freeze-dried dermis (8.32±0.37 J/cm ²) is slightly smaller than that of the wet dermis (9.65±1.21 J/cm²) due to the light absorption of water in wet tissues. Histological examinations were performed to evaluate the thermal damage and to find appropriate laser parameters for tissue micro-processing with minimal thermal damage. An analytical solution based on the heat conduction equation was derived to analyze the temperature distributions and to obtain the heat affected zones in materials ablated by USP laser line scanning. The analytical results were compared with the experimental measurements and a good agreement was found. Both results show that the thermal damage can be confined in a small zone about 10 μm with proper pulse energy and overlap rate. Pulse energy and pulse overlap rate were the key parameters for the generation and severity of thermal damage. In vitro wet tissue separation into layers by the USP laser ablation was demonstrated with thickness ranging from 200 to 600 μm. The unevenness of the separated layers is under 10%. Freeze-dried tissue stripping was also demonstrated with the stripped thickness in the range of 20 - 40 μm. No sign of visible thermal damage was found for both types of tissues. This study has provided an effective method that can precisely and non-intrusively process polymers and tissues with minimized thermal damage.