The prime minister told the Scottish Conservative party she would fight against any further decentralisation of power which meant the United Kingdom became "a looser and weaker union".
"Instead, they have an SNP Government obsessed with its own priority of independence, using the mechanisms of devolved government to further its political aims and all the while neglecting and mismanaging public services in Scotland".
The Conservative leader will also stress that it is a personal priority of hers to "strengthen and sustain the bonds that unite us". I believe passionately in the Union, I'm Prime Minister of the United Kingdom, but to me what matters is how we as politicians deliver for ordinary people in their day-to-day lives.
Scottish First Minister Nicola Sturgeon believes she has a "cast iron mandate" to hold a second ballot after the country voted to remain in the European Union past year but were overwhelmed by English votes to leave.
The prime minister's stance will be read by Sturgeon and the Scottish National party as an open challenge to call the threatened referendum on independence, suggesting the Tories are confident they can defeat the SNP.
"Her government has no mandate in Scotland, and no democratic basis to take us out of Europe and the single market against our will".
"We will always work to improve our public services - but absurdly ill-informed comments like this do the prime minister no favours".
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Sturgeon has called for Scotland to stay in the European Union single market, despite the United Kingdom voting to leave and a "hard Brexit" planned, warning another vote on independence is "all but inevitable" if that doesn't happen.
But Mrs May made clear the UK must not become a "looser and weaker Union", adding: "We can not allow our United Kingdom to drift apart".
Ms Sturgeon is threatening to call another indy vote, saying earlier this week that a second poll "would be a necessary way of giving the people of Scotland a say" in their future. "To me politics isn't a game".
And she will slam the SNP's performance on education, blaming failings on their "obsession" with a United Kingdom split. In return the UK Government's has so far been one of obstinacy and intransigence.
Opening the Scottish Conservative conference in Glasgow on Friday morning, the prime minister accused the Scottish government of "stoking-up endless constitutional grievance" at the expense of governing the country.
"It would offer Scotland a proper choice on whether or not to be part of a post Brexit UK - a UK that is undoubtedly on a fundamentally different path today than that envisaged in 2014".