Alexander Ponosov, the headmaster of a small school in the Urals, faces a lengthy prison sentence in a Russian jail after using illegally copied software.
Ponosov has said that he purchased computers with the software already installed and did not realise that his actions were illegal.
"A teacher who has dedicated his life to the education of children, and who receives a salary that does not bear comparison with the salaries of even regular staff in your company, is threatened with detention in Siberian prison camps," reads the open letter.
"We have great respect for the work of Microsoft's programmers and are in no way casting doubt on the principle of punishment for intellectual property violations.
"However, in this case, we ask you to show mercy and withdraw your complaint against Alexander Ponosov."
Current Russian premier Vladimir Putin said in a press conference last week that he saw no reason for the teacher to be jailed.
But Microsoft claims that it has no way of influencing the case since it is not involved, even though the pirating of its software is central to the case.
"This is a criminal case and as such was initiated and investigated by the public prosecutor's office in Russia," the software giant said in a statement.
"We are sure that the Russian courts will make a fair decision in Ponosov's case after a comprehensive analysis of all related details.
"Microsoft has no intention of making a civil claim against Ponosov. However, we do respect the Russian government's position on the importance of protecting intellectual property rights.
"Microsoft's anti-piracy efforts are focused on educating the market on the risk of counterfeit software and how to safeguard against purchasing counterfeit product, and enforcing against the creators and distributors of counterfeit software."
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